Our investigation of the mixed-function oxidases of rat liver microsomes has led to the following conclusions regarding their structure and function. Several species of cytochrome P450 exist in the endoplasmic reticulum (microsomes). One species of molecular weight 53,000 is induced by 3-methylcholanthrene. Another species of molecular weight 45,000 is induced by phenobarbital. A third predominates in control microsomes. These proteins make up a large part of the total microsomal protein. They are buried quite deeply in the lipid matrix of the membrane but a portion of each is exposed to the exterior. Each of the different types of cytochrome P450 is served by a single species of the reductase, NADPH-cytochrome P450 reductase. This reductase is attached to the membrane by a tail of about 70 amino acids. The remainder of the enzyme (70,000 daltons) is located on the exterior of the membrane such that it can be solubilized by proteases. This structure obviously allows the reductase to move about to serve all species of cytochrome P450. BIBLIOGRAPHIC REFERENCES: J. A. Buege and S. D. Aust. Comparative Studies of Rat Liver and Lung NADPH-cytochrome c Reductase. Biochim. Biophys. Acta 385 (1975) 371-379. A. F. Welton, F. O. O'Neal, L. C. Chaney and S. D. Aust. Multiplicity of Cytochrome P450 Hemoproteins in Rat Liver Microsomes. Preparation and Specficity of an Antibody to the Hemoprotein Induced by Phenobarbital. J. Biol. Chem. 250 (1975) 5631-5639.